Experimental evolution of aging in a bacterium

BMC Evolutionary Biology Experimental evolution of aging in a bacterium Martin Ackermann 1 2 Alexandra Schauerte 1 Stephen C Stearns 0 Urs Jenal 1 0 Department of Ecology and Evolutionary Biology, Yale University , New Haven, CT 06520-8106 , USA 1 Division of Molecular Microbiology , Biozentrum , University of Basel , CH-4056 Basel , Switzerland 2 Institute of Integrative Biology, ETH Zurich , CH-8092 Zurich , Switzerland Background: Aging refers to a decline in reproduction and survival with increasing age. According to evolutionary theory, aging evolves because selection late in life is weak and mutations exist whose deleterious effects manifest only late in life. Whether the assumptions behind this theory are fulfilled in all organisms, and whether all organisms age, has not been clear. We tested the generality of this theory by experimental evolution with Caulobacter crescentus, a bacterium whose asymmetric division allows mother and daughter to be distinguished. Results: We evolved three populations for 2000 generations in the laboratory under conditions where selection was strong early in life, but very weak later in life. All populations evolved faster growth rates, mostly by decreasing the age at first division. Evolutionary changes in aging were inconsistent. The predominant response was the unexpected evolution of slower aging, revealing the limits of theoretical predictions if mutations have unanticipated phenotypic effects. However, we also observed the spread of a mutation causing earlier aging of mothers whose negative effect was reset in the daughters. Conclusion: Our results confirm that late-acting deleterious mutations do occur in bacteria and that they can invade populations when selection late in life is weak. They suggest that very few organisms - perhaps none- can avoid the accumulation of such mutations over evolutionary time, and thus that aging is probably a fundamental property of all cellular organisms. - Background Aging seems paradoxical from an evolutionary perspective. Why is aging, which is detrimental for the individual, not eliminated by natural selection? Evolutionary theory provides an answer. Mutations that lead to aging are not efficiently removed by selection and can thus accumulate in populations over evolutionary time. Selection against these mutations is weak because under natural conditions, most individuals die for other, external reasons before aging manifests itself. This explanation hinges on two assumptions. First, such mutations must be detrimental late in life, but neutral [1] or beneficial [2] early on. If they were also detrimental early in life, they would be removed by selection. Second, the negative effects of age must be confined to old parents and to the progeny of old parents [3], while the progeny of young parents emerge rejuvenated. Rejuvenation refers to the fact that progeny are composed of newly synthesized organs, tissues, cells, and subcellular structures. As a consequence, they are less affected by the phenotypic deteriorations experienced by their aging parents. Without rejuvenation, negative effects would accumulate from generation to generation, and aging lineages would disappear [4]. Mutations with a negative effect that is specific for late age and can be rejuvenated in the progeny play a pivotal role in the evolution of aging. Any organism in which such mutations occur should evolve aging, whereas organisms in which such mutations do not occur should not age and should be potentially immortal. Initially, it was thought that such mutations can only occur in organisms with a distinction between soma and germline [4] where the negative effect of age would be confined to the soma and not be passed on to the progeny produced from the germline. Then, as anticipated by Weismann [5] the criterion for aging was expanded to any organism where the individuals emerging from reproduction are systematically different [6,7]. Aging has now been shown in unicellular eukaryotes [8,9] and even in bacteria [10,11]. As in other organisms, aging manifests in bacteria as decreasing performance with age. In bacteria, it is difficult to disentangle survival and reproduction, and it is thus not possible to use increasing mortality with age as an indicator for aging. Aging is thus quantified as a decline in the product of survival and reproduction [12] or as a decreasing growth rate with age [11]. According to the evolutionary explanation of aging, finding aging in bacteria suggests that mutations with deleterious effects specific to late life do occur in bacteria, and that they invaded populations over evolutionary times because selection late in life is weak. However, the existence of such mutations has yet to be demonstrated. That they do not necessarily occur is indicated by the failure to find them in viruses [13]. A second issue with such mutations is that they tie the evolution of aging to environmental conditions. One prediction is that fast aging should evolve if the strength of selection declines quickly with age, and slow aging if the strength of selection declines slowly. This prediction has been supported by a laboratory evolution experiment with fruit flies [14]. In this experiment, the decline in the strength of selection with age was varied by adjusting external mortality imposed by the experimenters. Another recent experimental study investigated the evolution of aging in natural populations of guppies living with or without predators [15]. The surprising outcome was that guppies in the presence of predators evolved slower aging. One plausible explanation for this result is that high extrinsic mortality does not always lead to weak selection late in life, because it may also cause a reduction in population density. If reduced population density benefits older individuals more than younger individuals, then increased extrinsic mortality might indeed improve the prospect of older individuals and thus lead to a slower decline in the strength of selection with age [16]. An alternative explanation is that if mutations with age-specific effects are rare, extrinsic risk does not easily modulate intrinsic aging. Here, we used experimental evolution with bacteria to test the evolutionary theory of aging at a basic level of biological organization: populations of unicellular organisms. Initially clonal populations were allowed to evolve under conditions where selection late in life was very weak. We then tested whether those populations would evolve earlier aging. This experiment is a stringent test of both the assumptions and the predictions of the evolutionary theory of aging. It tests both the assumption that mutations with a negative effect that is specific for late age and is subject to rejuvenation do occur, and the prediction that such mutations can increase in frequency under conditions where selection late in life is weak. If the assumptions of this theory are met in these asymmetrically reproduc (...truncated)